G protein coupled receptors (GPCRs) and Specialised Receptors

Vocabulary flashcards covering GPCR signaling and specialised receptor topics from Curtin Medical School lectures on GPCRs and enzyme-linked/nuclear receptors.

GPCRs

A superfamily of seven-transmembrane receptors that transmit signals via heterotrimeric G proteins and second messengers; ligands include hormones, neurotransmitters, peptides, lipids, and even light or touch.

First messenger

The ligand that binds to a GPCR to initiate signaling (e.g., hormones, neurotransmitters, light, scents).

Second messenger

A small intracellular molecule produced by effector enzymes (e.g., cAMP, IP3, DAG, Ca2+) that propagates the signal to downstream targets.

Biochemical amplification

Process by which a GPCR signal is magnified by producing many second messengers and activating downstream effectors.

Phosphorylation cascade

Sequential phosphorylation events that regulate target proteins and propagate GPCR signaling.

G protein

A heterotrimeric GTP-binding protein composed of alpha, beta, and gamma subunits that acts as a molecular switch in GPCR signaling.

G alpha subunit

The alpha subunit of G proteins; has GTPase activity and binds GDP in the inactive state; exchanges GDP for GTP to activate.

G beta-gamma subunit

Dimer that dissociates from G alpha upon activation and can independently regulate effectors such as phospholipase A2 and GIRK channels.

GTPase activity

Enzymatic activity that hydrolyzes GTP to GDP, turning off the active G alpha subunit.

GDP/GTP cycle

The cyclical exchange of GDP for GTP on G alpha during activation and subsequent return to the inactive state.

GIRK channels

G protein-gated inwardly rectifying potassium channels regulated by G beta-gamma to influence cardiac rhythm.

Gs alpha

Gs alpha subtype that stimulates adenylyl cyclase to increase cAMP.

Gi alpha

Gi alpha subunit that inhibits adenylyl cyclase, reducing cAMP.

Gq alpha

Gq alpha subunit that activates phospholipase C to generate IP3 and DAG.

G12/13 alpha

G12/13 activates Rho family GTPases.

Adenylyl cyclase

Enzyme activated by Gs that converts ATP to cAMP.

cAMP

Cyclic adenosine monophosphate; second messenger activating PKA.

PKA

Protein kinase A; cAMP-dependent kinase.

Phospholipase C

Enzyme activated by Gq that hydrolyzes PIP2 to IP3 and DAG.

IP3

Inositol trisphosphate; releases Ca2+ from stores; second messenger.

DAG

Diacylglycerol; activates PKC.

Ca2+

Calcium ions; intracellular messenger regulating many processes.

Beta-gamma signaling

G beta-gamma subunits can activate phospholipase A2 and certain ion channels (eg GIRK), sometimes independently of alpha.

G protein signaling cycle

Ligand binding → G protein activation → Effector activation → Second messenger formation → Amplification and propagation → Downstream functional changes → Biological response.

Receptor tyrosine kinases (RTKs)

Enzyme-linked receptors with intrinsic tyrosine kinase activity; ligands include growth factors; targets in cancer therapy.

Cross-linking

RTK activation via dimerization/oligomerization of receptor molecules.

Autophosphorylation

Phosphorylation of tyrosine residues within the RTK complex, activating signaling.

JAK/STAT pathway

RTK downstream signaling route that activates STAT transcription factors via phosphorylation.

RAS/MAPK pathway

RTK downstream signaling cascade regulating proliferation and differentiation.

Type I nuclear receptor

Cytosolic receptor bound to chaperone proteins; moves to the nucleus on ligand binding; forms homodimers; DNA-binding domain present; ligands include steroid hormones.

Type II nuclear receptor

Nuclear receptor bound to co-repressors; upon ligand binding co-repressors are released; heterodimerize with RXR; ligands include thyroid hormone and retinoic acid; DNA-binding domain present.

RXR (Retinoid X receptor)

Common dimerization partner for Type II nuclear receptors forming heterodimers.